Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Use of methylphenidate and reporting of valvular heart disease: Global pharmacovigilance analysis in children and adults.

INTRODUCTION: Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in relation with its micromolar affinity for the 5-HT2B receptor, whose activation may result in valvular heart disease (VHD). METHODS: To explore the association between the use of MPH and VHD reporting, we performed a disproportionality analysis within the WHO global safety database (VigiBase) using data, since inception until March 6th 2024, from: (i) the full database and (ii) different age groups (children/adolescents 6-17 years; adults 18-64 years). To avoid competition bias, safety reports with amphetamine-like appetite suppressants were excluded. Disproportionality was expressed using reporting odds-ratio (ROR) and its 95% confidence interval (CI). RESULTS: Of 29 129 spontaneous reports with MPH, 23 VHD cases (7.9 per 10 000 reports) were identified, including 13 adults and 10 children. Most cases concerned injury on the mitral valve. A disproportionate reporting was observed overall (ROR 1.6, 95% CI 1.1-2.4). Analysis according to age group found that disproportionality in VHD reporting was found in adults only (ROR 2.7, 95% CI 1.6-4.7) but not in children/adolescents (ROR 1.7, 95% CI 0.9-3.2). Furthermore, amongst MPH users only, VHD reporting was higher in adults compared to children (ROR 2.7, 95% CI 1.2-6.3). CONCLUSION: VHD reporting appears rare with MPH compared to other adverse events and is increased in adults only. Our findings support a potential safety signal of VHD in adults exposed to MPH. A risk in that population cannot be excluded and requires further assessment.

Common Seasonal Pathogens and Epidemiology of Henoch-Schönlein Purpura Among Children.

Importance: Henoch-Schönlein purpura (HSP) is the most common type of vasculitis in children. The factors that trigger the disease are poorly understood. Although several viruses and seasonal bacterial infections have been associated with HSP, differentiating the specific associations of these pathogens with the onset of HSP remains a challenge due to their overlapping seasonal patterns. Objective: To analyze the role of seasonal pathogens in the epidemiology of HSP. Design, Setting, and Participants: This cohort study comprised an interrupted time-series analysis of patient records from a comprehensive national hospital-based surveillance system. Children younger than 18 years hospitalized for HSP in France between January 1, 2015, and March 31, 2023, were included. Exposure: Implementation and relaxation of nonpharmaceutical interventions (NPIs) for the COVID-19 pandemic, such as social distancing and mask wearing. Main Outcomes and Measures: The main outcomes were the monthly incidence of HSP per 100 000 children, analyzed via a quasi-Poisson regression model, and the estimated percentage of HSP incidence potentially associated with 14 selected common seasonal pathogens over the same period. Results: The study included 9790 children with HSP (median age, 5 years [IQR, 4-8 years]; 5538 boys [56.4%]) and 757 110 children with the infectious diseases included in the study (median age, 0.7 years [IQR, 0.2-2 years]; 393 697 boys [52.0%]). The incidence of HSP decreased significantly after implementation of NPIs in March 2020 (-53.6%; 95% CI, -66.6% to -40.6%; P < .001) and increased significantly after the relaxation of NPIs in April 2021 (37.2%; 95% CI, 28.0%-46.3%; P < .001). The percentage of HSP incidence potentially associated with Streptococcus pneumoniae was 37.3% (95% CI, 22.3%-52.3%; P < .001), the percentage of cases associated with Streptococcus pyogenes was 25.6% (95% CI, 16.7%-34.4%; P < .001), and the percentage of cases associated with human rhino enterovirus was 17.1% (95% CI, 3.8%-30.4%; P = .01). Three sensitivity analyses found similar results. Conclusions and Relevance: This study found that significant changes in the incidence of HSP simultaneously with major shifts in circulating pathogens after NPIs for the COVID-19 pandemic indicated that approximately 60% of HSP incidence was potentially associated with pneumococcus and group A streptococcus. This finding suggests that preventive measures against these pathogens could reduce the incidence of pediatric HSP.

Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic.

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking. Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France. Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed. Exposure: Onset of COVID-19 pandemic. Main outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents). Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children. Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

In Utero Exposure to Antibiotics and Risk of Serious Infections in the First Year of Life.

INTRODUCTION AND OBJECTIVE: Given the high prevalence of antibiotic prescription during pregnancy in France and previous studies suggesting an increased risk of infection in offspring with such exposures, our study aimed to investigate the association between prenatal exposure to systemic antibiotics and serious infections in full-term infants during their first year of life. METHODS: We conducted a retrospective population-based cohort study on singleton, full-term liveborn non-immunocompromised infants, using the French National Health Data System (SNDS) between 2012 and 2021. Systemic antibiotic dispensing in ambulatory care settings during pregnancy defined the exposure. Outcomes concerned serious infections (i.e., infections requiring hospitalization) in offspring identified between 3 and 12 months of life, hence excluding infections of maternal origin. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariate models to control for potential confounders. RESULTS: Of 2,836,630 infants included, 39.6% were prenatally exposed to systemic antibiotics. Infants prenatally exposed to antibiotics had a higher incidence of serious infections compared with unexposed infants {aOR 1.12 [95% confidence interval (95% CI) 1.11-1.13]}. Similar associations were observed according to the timing of exposure during pregnancy, antibiotic class, and site of infections. The strongest association was observed when infants were prenatally exposed to three or more antibiotic courses during pregnancy [aOR 1.21 (95% CI 1.19-1.24)]. Limitations include residual confounders, such as genetic susceptibility to infections and the role of the underlying pathogen agent. CONCLUSION: Prenatal exposure to systemic antibiotics is very common and is associated with a weak yet significant associations with subsequent serious infectious events during the first year of life. While our study revealed associations, it is important to note that causation cannot be established, given the acknowledged limitations, including potential confounding by indication.